Improved intracochlear biopolymeric drug delivery system: an in vivo study

• Published in: Acta oto-laryngologica 2024-11, Vol.144 (11-12), p.581-7
• Main Authors: Goncalves, Stefania, Thielhelm, Torin, Pawley, Devon, Bas, Esperanza, Dikici, Emre, Deo, Sapna K, Dinh, Christine T, Daunert, Sylvia, Telischi, Fred
• Format: Article
• Language: English
• Subjects: Animals; Cochlea - drug effects; Dexamethasone - administration & dosage; Disease Models, Animal; Drug Delivery Systems; Ethacrynic Acid - administration & dosage; Evoked Potentials, Auditory, Brain Stem - drug effects; Injection, Intratympanic; Kanamycin - administration & dosage; Lactic Acid - administration & dosage; Male; Needles; Polyglycolic Acid - administration & dosage; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Inbred BN
• ISSN: 0001-6489; 1651-2251; 1651-2251
• DOI: 10.1080/00016489.2024.2412719

The delivery of drugs into the inner ear is a challenging field of study due to the complex cochlear anatomy and physiology. The creation of an intracochlear device that allows for short- and long-term intracochlear delivery of the drugs with a minimal invasive technology is needed to prevent or treat conditions that can potentially prevent the development of permanent hearing loss. This study intends to test the efficacy of DXM-infused PLGA microneedles created in our laboratory in an animal model of acute ototoxic injury. Twenty-four male Norway Brown rats were randomized into four groups, three of which groups received an intratympanic injection of ethacrynic acid and kanamycin. Two of these groups underwent the placement of an intracochlear microneedle blended or not with dexamethasone, and two groups underwent implantation of a plain microneedle, one of without prior exposure to the ototoxic agent to confirm biocompatibility. Animals were then followed with a weekly auditory brainstem response testing until day 28 after surgical intervention. Our intracochlear device demonstrated biocompatibility and produced no hearing changes after its implantation in the control group. Inserted DXM-blended microneedles prevented hearing deterioration in those animals exposed to an ototoxic environment.